Structure and function of renin and prorenin.

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1) X ray structure of reninThree-dimensional structure of mouse submaxillary renin and recombinant human renin have been determined at 2.5A^^ﾟ - 3.0A^^ﾟ resolution by X-ray analysis.2) Processing enzymesThe cDNA of prorenin processing enzyme in mouse submaxillary glands was cloned and its complete nucleotide sequence was determined, identify that prorenin processing enzyme is identical with proEGF processing enzyme. The processing enzyme processed the submaxillary prorenin to renin, but not kidney prorenin suggesting its organ specificity.Several candidates (yeast Kex2 like processing enzyme) for kidney prorenin processing enzyme or for prohormones and proenzymes have been identified and their complete amino acid sequences have been determined. These results suggests that not only prorenin but also prohormones and proenzymes are processed by substrate- or organ-specific manner.3) Gene regulation of renin and angiotensinogen in vivoHuman renin and human angiotensinogen genes both separately and in concert have been introduced into mice by cross-mating.Strains carring both the human genes demonstrated a chronically sustained increase in blood pressure. Thus, we have established new transgenic mice (Tsukuba Hypertensive Mice) as the first model of human high renin hypertension.